Our goal is the development of an inexpensive automated 4-color single- lane DNA sequencing machine adapted for mutation diagnostics in clinical environment using the p53 gene as a model system. Operation of the machine is based on a recently disclosed multicolor fluorescent detection technique which enables the detection and analysis low-power fluorescence signals. Main features of the machine: . analysis of contaminated DNA samples (10% resolution of wild and mutated admixtures); . high throughput (up to 500,000 bp/year); . low amount of labeled DNA material (10 times stretched ABI sequencing kit); . low cost of the machine In Phase I in collaboration with the Department of Electrical Engineering, SUNY Stony Brook, we shall develop an ultra-sensitive 4-color fluorescent detection system with data transfer rate of 1.6 Mbit/s and, in collaboration with the Department of Pathology SUNY SB, test this detection system using clinical DNA material. In Phase II we shall develop a pilot prototype of the machine entirely based on semiconductor components, integrated technologies, and low-power illumination sources and validate the machine using the p53 gene as a model system. In Phase III we shall organize manufacturing of the single-capillary machine and develop a 16-lane sequencer for diagnostic applications. PROPOSED COMMERCIAL APPLICATIONS: The proposed automated sequencing machine will find applications in clinical diagnostics of genetic disease, primarily cancer. its unique capability to precisely quantify contaminated DNA samples will ensure a dominant position in an important market segment. The low cost, miniature 4-colored automated machine with low consumption of labeled DNA material will be attractive for individual researchers and medical diagnostic laboratories.